Methods and devices for deploying and releasing a temporary implant within the body

ABSTRACT

Methods, devices and systems for delivering a device assembly into a gastric or other space within the body, allowing the device to expand to occupy volume within the gastric space and, after an effective period of time, delivering a substance or stimulus to begin breakdown of the expanded device so that it may release from the body.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. application Ser. No.13/773,516, filed Feb. 21, 2013 which claims benefit of priority to U.S.Provisional Application Nos. 61/762,196 entitled Thermally DegradableBiocompatible Constructs and Methods of Degrading filed Feb. 7, 2013;61/601,384 entitled Swallowed Intragastric Balloon Filled via NarrowExtracorporeal Tube filed Feb. 21, 2012; 61/645,601 entitled DeliveryString for Gastrointestinal Applications filed May 10, 2012; 61/647,730entitled Hydrogel Driven Valve filed May 16, 2012; 61/663,433 entitledFluid Transfer Device for Hydrogel Constructs filed Jun. 22, 2012;61/663,682 entitled Hydrogel Driven Valve filed Jun. 25, 2012;61/663,683 entitled Fluid Transfer Device for Hydrogel Constructs filedJun. 25, 2012; No. 61/674,126 entitled Payload Delivery System andMethod filed Jul. 20, 2012; and 61/699,942 entitled System for RapidHydrogel Construct Degradation filed Sep. 12, 2012, the entirety of eachof which is incorporated by reference.

BACKGROUND OF THE INVENTION

The present invention generally relates to the field of devices thattemporarily occlude spaces within the body to provide a therapeuticeffect.

According to 2010 World Health Organization data, 198 million Americansover the age of 15 are above target weight. Of these individuals, 89million are considered overweight (25<Body Mass Index<30) and 109million are considered obese (Body Mass Index>30). Worldwide, more than1.4 billion adults age 20 and over are overweight, and 500 million areobese. Obesity places patients at increased risk of numerous,potentially disabling conditions including type 2 diabetes, heartdisease, stroke, gallbladder disease, and musculoskeletal disorders1,2,3. Compared with healthy weight adults, obese adults are more thanthree times as likely to have been diagnosed with diabetes or high bloodpressure4. In the United States it is estimated that one in fivecancer-related deaths may be attributable to obesity in femalenon-smokers and one in seven among male non-smokers (>=50 years of age).On average, men and women who were obese at age 40 live 5.8 and 7.1fewer years, respectively, than their healthy weight peers.

Gastric bypass surgery is the current gold standard treatment forpatients with a body mass index (“BMI”) of greater than 40. Gastricbypass surgery is also an option for those with a BMI between 35-39 withobesity-related co-morbidities. While gastric bypass surgery results indecreased food consumption and weight loss for a majority of recipients,it requires life-altering, permanent anatomic modifications to thegastrointestinal tract and can result in severe complications. Gastricbypass and related surgical procedures are also expensive, costing about$22,500 (by laparoscopy). For these reasons, only about 250,000 surgicalobesity procedures are performed per year in the US.

For the vast majority of the overweight and obese population for whomsurgical obesity procedures are not appropriate, few efficacious andaffordable interventions are currently available. Diet and exerciseremain the front line approaches to obesity, however this approach hasat best slowed the growth of the epidemic. To date, drug therapies havedose limiting side effects or have lacked meaningful long term efficacy.

One less-invasive intervention that has begun to gain popularity is anintragastric balloon. Intragastric balloons can be placed endoscopicallyor positioned using other methods and generally must be removedendoscopically or rely on the body's natural digestive processes forremoval.

The devices, methods, and systems discussed herein are intended toprovide an effective treatment for obesity. Moreover, the devices,methods, and systems described herein are not limited to any particularpatient population and can even be applied to clinical areas outside ofobesity.

SUMMARY OF THE INVENTION

The present invention relates to devices and methods for occupying aspace within a patient's body. In particular, the devices and methodscan be used within a gastric space. However, the devices and methods canbe used in any part of the body.

In a first example, a medical device under the present disclosureincludes a device assembly comprising a skin, a fluid transfer member,and a release material, the skin forming a perimeter of the deviceassembly defining a reservoir therein, where the release material iscoupled to at least a portion of the skin such that the skin and releasematerial are coupled to create a physical barrier about the reservoir,where the skin is liquid impermeable and where the fluid transfer memberpermits delivery of fluids into the reservoir through the physicalbarrier; the device assembly having a deployment profile and an activeprofile, where the deployment profile is smaller than the active profileand permits deployment of the device assembly within a gastric space inthe patient's body; a filler material retained within the reservoir bythe physical barrier and configured to expand as fluid is deliveredthrough the fluid transfer member to cause the device assembly to expandfrom the deployment profile to the active profile such that the deviceassembly occupies at least a portion of the gastric space within thepatient's body; wherein exposure of the release material to an exogenoussubstance opens at least one path in the physical barrier such that thefiller material can pass into the patient's body resulting in reductionof a size of the deployment profile. As noted herein, an exogenousmaterial, substance, and/or stimuli as used herein can comprise anymaterial or substance that is not normally found within the patient'sbody (or has a condition not normally found within the patient's body,including duration). In most cases the exogenous material, substanceand/or stimuli originate from outside the patient's body. In manyvariations, such an exogenous trigger allows for control over theduration of time that the device is located within the body. In somevariations, the exogenous material is the fluid used to fill thereservoir initially (for example, a fluid with a certain osmolality).One such benefit is that, as body chemistry varies between populationsof potential patients, the use of exogenous triggers reduces thevariability of the duration of device placement and improve patientoutcomes as a result of the devices, methods, and systems that rely onsuch exogenous triggers.

Variations of the devices and methods herein can include two possiblemanifestations: a) the degradation occurs over time but is exquisitelycontrolled by choice of filler fluid and release material and theinitial conditions inside the device; and/or b) the degradation occurson-demand via introduction of exogenous stimulus following deployment.

The fluid transfer member can include any number of components from asimple orifice in a skin of the device, to a conduit or wick member. Thefluid transfer member can also optionally include a sealable fluid path.

In another variation of the device, the fluid transfer member furthercomprises a conduit having a proximal end and a device end, where thedevice end of the conduit is flexible to accommodate swallowing by thepatient and the conduit is coupled to the sealable fluid path, where alength of the conduit permits delivery of fluid into the reservoir whenthe device assembly is located within the patient's body and theproximal end is positioned outside of the patient's body. The device canalso include a conduit that is detachable from the sealable fluid pathwhen pulled away from the sealable path, wherein the sealable path isconfigured to form an effective seal upon removal of the conduit.

In certain variations, the sealable fluid path is configured to collapseto be substantially sealed when the device assembly assumes the activeprofile and the conduit is detached from the sealable fluid path.

An additional variation of the device further comprises anelongated?conduit having a proximal end and a device end, where thedevice end is flexible to accommodate swallowing by the patient, wherethe sealable fluid path comprises a flexible elongate tunnel extendingfrom the reservoir to an exterior of the skin, where the device end ofthe conduit is removably located within the flexible elongate tunnelstructure, such that upon removal of the conduit the flexible elongatetunnel structure increases a resistance to movement of substances therethrough to form a seal.

Fluid transfer members described herein can further comprise a wickelement where a first end of the wick element is in fluid communicationwith the reservoir and a second end of the wick element extends out ofthe sealable fluid path such that when positioned within the stomach ofthe patient, the wick draws fluid from the stomach of the patient intothe reservoir.

In some variations, the fluid path is configured to compress the wickelement to seal the fluid path as the device assembly assumes the activeprofile. In additional variations, the wick element withdraws into thereservoir as the device assembly assumes the active profile such thatthe fluid path seals as the filler material expands within thereservoir.

Variations of the device include skins having at least one opening andwhere each of the at least one openings are covered by the releasematerial. For example, the release material can comprise a plurality ofdiscrete portions covering a plurality of openings in the skin. At leasta portion of the release material can optionally comprise a shape thatapproximates a shape of the deployment profile, reducing the amount ofdeformation of the release material.

In additional variations, a portion of the skin defining an opening ismechanically bound together by a portion of the release material toclose the physical barrier. For example, in certain embodiments at leasttwo edges of the skin are located on an interior of the device assembly.

Devices of the present disclosure can include one or more releasematerial(s) located on an interior of the reservoir such that therelease material is physically separated from bodily fluids.

The filler material used in any of the devices or methods disclosedherein can comprise, when expanded, a semi-solid consistency similar tonatural substances within the body.

The present disclosure also includes methods for temporarily occupyingspace in a body of a patient, such as in a gastric region or other areaof the body. Such a method can include providing a device assemblyhaving a conduit comprising a flexible end portion free of rigid and/orsemi-rigid materials to enable swallowing of the device assembly and theflexible end portion, where the flexible end portion has an end thatextends within a reservoir of the device assembly; deploying the deviceassembly within the gastric space (where deploying can optionallyinclude directing or inducing a patient to swallow the device);delivering a fluid through the supply tube such that the device assemblyexpands to an active profile that occupies a sufficient volume withinthe gastric space to provide a therapeutic effect; and withdrawing thesupply tube from the device assembly allowing the device assembly toself seal and permit the device assembly to remain within the gastricspace for a period of time. In some variations, deploying the deviceincludes directing a patient to swallow the device assembly whileoptionally maintaining control of the proximal end of the conduitoutside the body.

The method described herein can also include a device assembly thatfurther comprises a liquid impermeable skin material that is coupled toa release material to form a physical barrier, the method furthercomprising delivering an exogenous substance to the gastric space thatcauses disruption of the release material and allows the device assemblyto reduce in size.

The exogenous substance can optionally comprise a fluid having atemperature greater than body temperature. The exogenous substance canoptionally comprise a material that raises a temperature within thegastric space, which causes disruption of the release material. Inadditional variations, the exogenous substance can be present in thefiller fluid, often with the intention of causing a predicted buttime-delayed trigger of the release material.

In another variation of the method, the device assembly furthercomprises a filler material within the reservoir that expands whencombined with the fluid, where delivering the fluid comprises deliveringthe fluid until the combination of fluid and filler material expands thedevice assembly to the active profile.

Another variation of the method includes deploying a plurality of deviceassemblies such that the plurality of device assemblies occupies avolume to provide the therapeutic effect.

In an additional variation, a method for temporarily occupying a spacein a body of a patient can include: providing a device assembly having ahydroscopic member extending from an exterior of the device assemblyinto a reservoir of the device assembly, a filler material locatedwithin the reservoir where the device assembly and hydroscopic memberare capable of being swallowed by the patient; wherein after positionedwithin the gastric space, the hydroscopic member absorbs fluids withinthe gastric space and delivers the fluids into the reservoir such thatthe fluids combine with the filler material to expand the deviceassembly into an active profile until the device assembly self-seals;and delivering a substance to the gastric space to cause a portion ofthe device assembly to degrade and allow the expanded filler material toescape from the reservoir and pass within the body of the patient.

Another variation of a device of the present disclosure can include adevice assembly comprising a skin, a fluid transfer member, the skinforming a perimeter of the device assembly defining a reservoir therein,where the skin is liquid impermeable and where the fluid transfer membercomprises a flexible elongate fluid path that permits delivery of fluidsinto the reservoir; the device assembly having a deployment profile andan active profile, where the deployment profile is smaller than theactive profile and permits positioning of the device assembly within thepatient's body via swallowing of the device assembly; a filler materialretained within the reservoir and configured to expand as fluid isdelivered through the fluid transfer member to cause the device assemblyto expand from the deployment profile to the active profile such thatthe device assembly occupies at least a portion of the gastric spacewithin the patient's body; and an elongate conduit having a proximal endand a device end, where the device end is flexible to accommodateswallowing by the patient, the elongate conduit configured to deliverfluid through the fluid transfer member, where the device end of theconduit is removably located within the flexible elongate fluid path,such that upon removal of the conduit the flow resistance of theflexible elongate fluid path is sufficient to prevent filler materialfrom escaping.

In another variation, a medical device for occupying a space within apatient's body comprises a device assembly comprising a skin, a fluidtransfer member, and a release material, the surface layer forming aperimeter of the device assembly defining a reservoir therein, where therelease material is coupled to at least a portion of the skin such thatthe skin and release material form a physical barrier about thereservoir and where the fluid transfer member comprises a flexibleelongate valve extending within the reservoir; a conduit having aproximal end extending from outside of the perimeter of the deviceassembly and a flexible device end extending through flexible elongatevalve, the flexible device end having a compliance to permit swallowingof the device end and device assembly; a filler material retained withinthe reservoir by the physical barrier and configured to expand as fluidis delivered through the fluid transfer member to cause the deviceassembly to expand from a deployment profile to an active profile suchthat the device assembly occupies at least a portion of the gastricspace within the patient's body in the active profile; wherein theconduit device end is removable from the flexible elongate valve uponassuming the active profile, wherein upon removal of the device end fromthe flexible elongate valve, a flow resistance of the flexible elongatevalve prevents filler material from escaping therethrough; and whereinexposure of the release material to a substance not naturally producedin the body disrupts the release material in a predictable manner andopens at least one path in the physical barrier.

Another variation of a medical device for occupying a gastric spacewithin a patient's body comprises: a device assembly comprising a skinand a fluid transfer member, the surface layer forming a perimeter ofthe device assembly defining a reservoir therein; a conduit having aproximal end extending outside of the perimeter of the device assemblyand a device end extending through the fluid transfer member such thatthe conduit is in fluid communication with the reservoir, wherein theconduit comprises a hydroscopic material that pulls fluid from thegastric space into the reservoir; and a filler material retained withinthe reservoir by the physical barrier and configured to expand as fluidis delivered through the fluid transfer member to cause the deviceassembly to expand from a deployment profile to an active profile suchthat the device assembly occupies at least a portion of the gastricspace within the patient's body in the active profile, wherein in theactive profile the expanded filler material causes closure of the fluidtransfer member to prevent the conduit from pulling fluid into thereservoir.

In yet another variation, the entire skin can comprise a releasematerial such that an exogenous trigger causes disruption of the entiredevice to begin the breakdown process.

Another variation of a device for occupying a space within a patient'sbody includes a device assembly comprising a skin, a fluid transfermember, and a release material, the skin forming a perimeter of thedevice assembly defining a reservoir therein, where the release materialis coupled to at least a portion of the skin such that the skin andrelease material are coupled to create a physical barrier about thereservoir, where the skin is liquid impermeable and where the fluidtransfer member permits delivery of fluids into the reservoir throughthe physical barrier; the device assembly having a deployment profileand an active profile, where the deployment profile is smaller than theactive profile and permits deployment of the device assembly within agastric space in the patient's body; whereupon fluid entering thereservoir causes the device assembly to expand from the deploymentprofile to the active profile such that the device assembly occupies atleast a portion of the gastric space within the patient's body; andwherein application of an exogenous substance opens at least t one pathin the physical barrier such the fluids exit the reservoir resulting inreduction of a size of the deployment profile.

The devices described herein can also be used for delivery of drugs,pharmaceuticals, or other agents where such items can be delivered on askin of the device, within a reservoir, in a filler of the device, oranywhere on the device. Such agents can be released over time.

The above and other features of the invention including various noveldetails of construction and combinations of parts, and other advantages,will now be more particularly described with reference to theaccompanying drawings and pointed out in the claims. It will beunderstood that the particular method and device embodying the inventionare shown by way of illustration and not as a limitation of theinvention. The principles and features of this invention may be employedin various and numerous embodiments without departing from the scope ofthe invention.

BRIEF DESCRIPTION OF THE DRAWINGS

The foregoing and other objects, features and advantages of the methods,devices, and systems described herein will become apparent from thefollowing description in conjunction with the accompanying drawings, inwhich reference characters refer to the same parts throughout thedifferent views. The drawings are not necessarily to scale; emphasis hasinstead been placed upon illustrating the principles of the invention.Of the drawings:

FIG. 1A, illustrates an example of a gastric device assembly prior toassuming an active profile.

FIGS. 1B and 1C show partial cutaway views of examples of deviceassemblies for use in occupying space within a body.

FIG. 1D illustrates the variation of the device shown in FIG. 1A as thedevice assembly assumes an active profile.

FIG. 1E shows a device assembly after it is inflated, expanded, orotherwise transitioned to achieve a desired active profile.

FIG. 1F illustrates a state of a device assembly after a physician,patient, or other caregiver desires to initiate release the deviceassembly from the body.

FIG. 2 shows a device assembly or construct in a hydrated or activeprofile whose outer “skin” defines a material reservoir or pocket.

FIGS. 3A to 3E illustrate additional variations of device assemblies 100having various active profiles.

FIG. 4 illustrates a variation of a fluid transfer member also having asealable fluid path for use with the device assemblies described herein.

FIG. 5 shows a variation of a tunnel valve.

FIG. 6A illustrates a partial view of a variation of an invaginatedsection of a skin of a device assembly.

FIGS. 6B and 6C illustrates a partial view of the interior of a deviceassembly comprising an invaginated section of the skin further havingenergy storage element that assists in opening of the device in responseto an exogenous trigger.

FIG. 6D provides a schematic illustration of another example of a deviceassembly having a release material located on a surface of the skin.

FIGS. 7A and 7B show one example of an exploded, assembly view of adevice assembly.

FIGS. 8A and 8B show an additional variation of a portion of a deviceassembly that provides a control over the fluid permeable path throughotherwise impermeable material surface.

FIG. 9A shows another aspect of devices as described herein comprisingone or more fluid transport members.

FIG. 9B also illustrate a device having a delivery system attachedthereto.

FIGS. 10A and 10B an example of a valve driven by expansion of fillermaterial within a reservoir of the device assembly.

FIGS. 10C and 10D show another variation of a valve.

FIG. 10E shows a hybrid valve wherein each hybrid flow control layer isgenerally rectangular and the impermeable region and permeable regionare triangular.

FIG. 10F shows an exploded view of a valve assembly, a permeable regionin one individual flow control layer may be, for example, a circularregion, and the impermeable region may be an annulus disposed around thecircular permeable region.

FIG. 11A illustrates another variation of a device having a fluidtransport member that comprises a fluid wick that extends into areservoir of the device.

FIG. 11B shows the exterior segment of liquid wick structure immersed ina liquid causing liquid to be drawn into the absorbent wick material ofliquid wick structure and further drawn from the wet wick.

FIG. 12A, shows an exemplary embodiments of liquid wick structurefluidly coupled to a secondary, interior bag, pouch, or other container.

FIG. 12B illustrates another embodiment of a device having multipleliquid wick structures.

FIG. 12C, shows an interior segment of a single liquid wick structurethat is divided into two or more sub-segments.

FIG. 12D shows a wick structure affixed to a portion of the interior ofthe reservoir.

FIG. 13A illustrates a variation of a tunnel valve as discussed abovethat forms a sealable fluid path preventing material from escaping fromthe interior of the device.

FIG. 13B shows a cross sectional view of tunnel taken along line 13B-13Bof FIG. 13A.

FIG. 13C shows the tunnel closing.

FIG. 14 shows a device assembly compressed to fit within an oral dosageform such as a pill, capsule, sleeve, or other form that enhances theability of positioning the device via ingestion or swallowing withoutthe aid of another medical device.

FIG. 15A shows hydrogels comprised of either cross-linked polyacrylicacid or cross-linked polyacrylamide, materials that are widely used inmedical device applications.

FIG. 15B shows cross-linked polyacrylic acid or cross-linkedpolyacrylamide, materials that are widely used in medical deviceapplications.

FIG. 15C depicts the swelling performance of a chitosan/poly(vinylalcohol) superporous hydrogel in solutions at different pHs.

DETAILED DESCRIPTION OF THE INVENTION

The following illustrations are examples of the invention describedherein. It is contemplated that combinations of aspects of specificembodiments or combinations of the specific embodiments themselves arewithin the scope of this disclosure. While the methods, devices, andsystems described herein are discussed as being used in the stomach orgastric space, the devices, methods, and systems of the presentdisclosure can be can be used in other parts of the body where temporaryocclusion of a space might be required or beneficial. The presentdisclosure is related to commonly assigned US Publication No.2011/0295299 filed Mar. 2, 2011 and PCT/US2013/027170, the entirety ofboth which are incorporated by reference.

FIG. 1A, illustrates an example of a gastric device assembly 100. Inthis example, the gastric device assembly or construct 100 can reside ina stomach (typically of a mammal) for an extended period of time. Onebenefit of such a device is that, when partially or fully deployed, theconstruct 100 occupies volume within the stomach to produce atherapeutic effect, e.g., to stimulate the sensation of satiety, andresists passage from the body by normal body function. As illustratedbelow the construct generally comprises three states: a pre-deploymentconfiguration (FIG. 1A); a deployed or active configuration (FIG. 1D,1E); and a release configuration (FIG. 1F). As noted above, the devicecan also be used for therapeutic benefits that do not involve occupyingvolume (e.g., drug delivery, creation of a cavity by separating adjacenttissue, etc.).

FIG. 1A illustrates a variation of the device 100 after placement withina stomach 2. As described herein, the initial configuration of thedevice 100 includes a compact state that allows placement within thebody. The device can be in a pill-type configuration or any other shapethat permits swallowing. Alternatively, the device 100 can be positionedby the use of a scope type device, catheter, or other medicalpositioning device.

For a device used in the digestive tract/gastric space, the deviceassembly 100 can be positioned within the body either by naturalingestion or the use of a delivery system (such as a catheter,endoscope, or other medical device). The delivery system can optionallycomprise an oral dosage form, not illustrated, which facilitates theingestion of a relatively large object. In other embodiments the systemcomprises a tether that allows manipulation or control of the placedconstruct from outside of the body. The assembly 100 can also be placedin the stomach by more invasive surgical or endoscopic procedures.

In FIG. 1A, the device 100 is shown immediately after being deployedwithin the stomach 2 and is ready to be activated. As noted herein, thedevice 100 can be deployed in the configuration shown. Alternatively,the device can be contained within a capsule or pill-type casing thatallows for swallowing by a patient. Once swallowed, the casing willreadily dissolve or break down resulting in the configuration shown.Once in place in the stomach, the assembly 100 begins to expand in orderto occupy volume/space within the body. Expansion can occur via manualinflation, including hydration or other activation of a filler material(as shown optionally using a catheter, inflation tube or other deliverysystem), via absorption of body fluids, via remote actuation of asubstance already located within the device assembly, and/or deliveringof a fluid into the assembly, where the fluid itself causes expansion.Variations of the device also include a combination of such expansionmeans.

The variation shown in FIG. 1A includes a member 110 that extends fromthe device 100 to outside of the patient. In this variation shown, themember 110 comprises a fluid transport member that is fluidly coupled toan interior of the device 100 allowing for the delivery of substancesand/or fluids within the device 100. FIG. 1A shows an exemplary fluidsource 90 coupleable to a variation of a fluid transport member 110 suchthat the delivery of fluid causes a filler material 108 within thedevice to expand. In the illustrated example, the fluid transport membercomprises a conduit. However, alternate variations of the devicesdescribed herein include fluid transport members that reside within thepatient's body. Alternate variations of the device 100 also includemembers 110 that function as delivery or positioning systems to ensureproper placement of the device 100 within the body. Such deliverysystems may or may not be fluidly coupled with an interior of thedevice. In variations discussed below, the device can include one ormore fluid transport members that remain within the body but stillconvey fluid into the device 100 to allow the device to assume an activeprofile.

FIG. 1B shows one a partial cutaway view of an example of a deviceassembly 100 for use in occupying space within a body. In thisvariation, the device assembly 100 includes a material surface or skin102 that forms a reservoir or pocket 104 capable of retaining a varietyof substances, including but not limited to fluids, solid substances,semi-solid substances, etc. In the illustrated variation, the reservoir104 holds a filler material 108 such as dehydrated hydrogel granulesthat can swell in size upon the addition of a fluid. However, any numberof substances can be contained within the reservoir 104. Alternatevariations of the device and/or method include assemblies that do notinclude a filler material; rather a filler material can be depositedwithin the reservoir 104 once the assembly is deployed. Alternatively,or in combination, the reservoir can be filled with a gas, liquid orother gel type substance.

In other variations, the device assembly 100 can include an emptyreservoir that can be deployed into the body and subsequently filledwith a filler material or other substance. For example, such variationscan include a liquid filler material that is delivered to the reservoirthrough a conduit. The volume of liquid required to expand the deviceinto a desired active profile can pre-determined. In some variations,the volume can be determined by measuring the back pressure in theconduit or pressure within the reservoir using any number of pressuredetecting elements.

FIG. 1B also illustrates a variation of a sealable fluid path 112coupled to and/or forming part of the fluid transfer member. In thisexample, the sealable fluid path 112 extends outside of the perimeter ofthe skin 102 of the device 100. Additional variations of the device 100can include significantly shortened sealable fluid paths 112. In yetadditional variations, the device assembly 100 can omit the sealablefluid path 112.

As noted herein, the skin 102 includes a release material 106 coupledthereto, where the release material 106 allows for initiating release ofthe assembly 100 from the body shortly after degradation, activation, orbreakdown of the release material. Once the device assembly 100 is inthe active profile, it can remain in the active profile for apre-determined amount of time or until the patient experiences a desiredtherapeutic effect. To initiate release of the device assembly 100 fromthe body, an exogenous material, substance or stimulus is administeredto the patient. The substance can comprise a fluid or other activatingagent having properties that either directly or indirectly act on therelease material to disrupt the barrier and allow the contents of thereservoir to be exposed to the body. For example, the exogenoussubstance can comprise a heated fluid that melts the release material.Alternatively, the exogenous material can change a temperature and/or anacidity of fluids in the stomach such that the enhanced properties ofthe fluids begin to act, either directly or indirectly, upon the releasematerials. In additional variations, the release material can comprise amaterial or materials that effectively form a barrier as discussedherein and are separated or disengaged by the use of an exogenousstimuli (e.g., a magnetic field, ultrasound, IR heating, coherent light,electromagnetic signals, microwave field, etc.).

FIG. 1B also illustrates a variation where the release material 106 isin the form that approximates shape and/or size of the casing used todeliver the device 100 (in this example the release material 106 is in apill shape). One benefit of such a configuration is that the releasematerial 106 can be positioned within the casing without excessivefolding or bending.

FIG. 1C illustrates a sectional view of another variation of a deviceassembly 100. In this variation, the release material 106 binds orotherwise joins edges of the skin from within the reservoir 104. Such aconfiguration protects the release material 106 from the localenvironment of the body (e.g., fluids within the stomach or digestivetract). The release material can still be activated and/or degraded bythe addition of the exogenous material to the body as described herein.However, positioning of the release material within the reservoirpermits the skin 102 to serve as an additional layer of protection toprevent inadvertent release of the device assembly 100. The releasematerial 106 can comprise a layer that binds edges of the skin together.

FIG. 1C also illustrates a variation of a sealable fluid path 112. Inthis example, the sealable fluid path 112 does not extend outside of theperimeter of the skin 102. Additional variations of the device 100 caninclude significantly shortened sealable fluid paths 112. In yetadditional variations, the device assembly 100 can omit the sealablefluid path 112.

FIG. 1D illustrates the variation of the device 100 shown in FIG. 1A asthe device assembly 100 assumes an active profile. An active profileincludes any profile apart from a deployment state and where the profileallows the device to perform the intended effect of occupying volume orspace within the body to produce a therapeutic effect. In theillustrated example, a physician or other medical practitioner deliversfluid via the fluid transport member 110, comprising a conduit 114 inthis variation, and into the reservoir 104 causing a filler material 108to swell. As noted herein, other variations include device assemblieswithout filler material where the conduit 114 simply delivers fluid andor other substances that allow the device assembly to achieve an activeprofile.

When using a conduit 114 that extends outside of the body, a physiciancan deliver a hydrating liquid, such as water or distilled water throughthe conduit 114. Generally, a pre-determined volume of liquid can bemanually or mechanically pumped into the exterior end of the conduitwherein the volume of liquid is pre-determined based on a particularsize of the device assembly or based on a desired active state. In somevariations, the volume of liquid can also depend on the length ofconduit.

The conduit 114 can be used to transfer a substance or into thereservoir 1014 of the device. In the illustrated variation, the conduit114 transfers fluid from outside of the patient's body into thereservoir 104 after deployment of device assembly 100 within the body.Alternatively, or in combination, a fluid transfer member can comprise awick type device that transfers liquids or other fluids from within thebody to the reservoir.

FIG. 1E shows the device assembly 100 after it is inflated, expanded, orotherwise transitioned to achieve a desired active profile. A physiciancan monitor the profile of the device assembly 100 either using a scopepositioned within the stomach (not shown) or non-invasive imaging suchas ultrasound or a radiographic imaging. Alternatively, or incombination, the active profile can be achieved after a pre-determinedvolume of fluid, liquid and/or gas is delivered to the reservoir 104.Furthermore, variations of the device can include one or more markers(such as radiopaque markers) 116 allowing a physician to determineorientation and/or size of the device assembly 100.

As noted above, this particular variation of the assembly 100 includes aconduit 114 that is coupled to the skin 102 through the fluid path 112and extends into the reservoir 104. Alternatively, a conduit 114 can bedirectly coupled to the skin. When the device assembly 100 achieves theactive state the conduit 114 can be pulled from the device assembly 100.For those variations that employ a sealable fluid path 112, withdrawalof the conduit 114 causes the sealable fluid path 112 to collapse or becompressed thereby preventing the contents of the reservoir 104 fromescaping from the device assembly 100. Alternatively, or in combination,the sealable fluid path 112 located within the reservoir 104 can besealed due to the increased pressure within the reservoir. In otherwords, the same pressure within the reservoir 104 that causes expansionof the device 100 also causes the sealable fluid path 112 to close,compress or otherwise reduce in diameter to a sufficient degree thatmaterial is unable to escape from the reservoir through the sealablefluid path 112.

In certain variations, the conduit 114 is held in place in the sealablefluid path 112 by friction alone. Withdrawal of conduit occurs bypulling on the conduit in a direction away from the device 100. Duringthe initial stages of this withdrawal activity the expanded device 100generally moves upwardly with the conduit in the stomach, until theexpanded device 100 reaches the esophageal sphincter. With the deviceassembly restrained from further upward movement by the sphincter, theconduit 114 may then be withdrawn from the fluid path and from thepatient by additional pulling force.

Upon withdrawal of conduit 114 the fluid path effectively seals, asdescribed herein, and prevents migration of fluids or other substancesinto and out of the reservoir. In certain variations the fluid pathseals on its own after removal of a conduit or other member locatedtherein. In additional variations, hydrostatic pressure and/or pressurecaused by the expanded filler acting along the length of the fluid pathcan aid in sealing of the fluid path.

FIG. 1F illustrates a state of the device assembly 100 after a physicianor the patient desires to initiate release the device assembly 100 fromthe body. As discussed above, an exogenous material 120 is deliveredinto the stomach (or other portion of the body as applicable). As theexogenous material 120 (or exogenously activated body fluids) engage therelease material 106, the release material reacts to the conditionscreated by the exogenous material and begins to degrade, melt, breakdown, or otherwise become unstable such that the physical barrier of theskin 102 becomes compromised. As noted above, additional variations ofthe devices can be used with an exogenous stimulus in place of or inaddition to an exogenous material. For example, the exogenous substancecan directly act upon the release material such as providing a substanceat an elevated temperature and/or PH level that causes disruption of therelease material to allow the filler material to interact with thefluids in the stomach and/or to pass from reservoir into the stomach.Alternatively, the exogenous material can interact with fluids withinthe body to directly or indirectly activate and/or degrade the releasematerial.

In alternate variations, the release material, or additional areas onthe skin degrade or become unstable due to the passage of time in thenormal gastric environment. In such cases, the additional areas canserve as a safety mechanism to ensure release of the device after apre-determined period of time. For example, in the variation shown inFIG. 1F, one of the areas of release material 106 can be responsive toexogenous stimulus or exogenous materials while the other releasematerial 106 can break down over time. Alternatively, or in combination,as shown in FIG. 1F an exogenous stimuli can be used in combination withthe exogenous material 120 to cause disruption of the release material.In another variation, the exogenous stimuli 130 can be used to actdirectly on the release material 106 (without any exogenous material) tocause disruption of the release material 106 and to begin the process ofreleasing the device assembly 100 from the patient.

FIG. 1F illustrates the filler material 108 escaping from the reservoir104 as the device assembly 100 decreases from its active profile toallow for passage of the skin 102 and filler material 108 from the body.In certain variations, the consistency of the escaping filler material108 is similar to or closely approximates the consistency of a foodbolus. The matching of the consistency of the filler material tonaturally occurring particles that travels within the body ease thepassage of the filler material 108 through the remainder of thedigestive tract. In certain situations, the instability or degradationof the release material 106 allows bodily fluids to mix with the contentof the reservoir 104, which liquefies the filler material and expeditesreduction of the device assembly 100 from an active profile or state.Although not illustrated, as the device assembly reduces in profile, theperistaltic movement of the muscles in the digestive tract works toextrude materials out of the device 100, allowing for the passage of theskin 102 of the device 100 through the digestive tract until it isultimately excreted from the body. Certain variations of the deviceassembly can be made to have a soft, lubricious and/or malleableconfiguration to aid in passing through the gastrointestinal tract.

FIGS. 1A to 1F are intended to illustrate variations of devices andmethods for occupying space within a patient's body, especially thosedevices for use within a gastric space. However, the principlesdescribed above can be used with any number of variations of the deviceas described below. As noted herein, combinations of differentvariations of devices, as well as the combinations of aspects of suchvariations are considered to be within the scope of this disclosurewhere such combinations do not contradict one another.

In the embodiment shown in FIG. 2 the construct 1000 is in a hydrated oractive profile and comprises a generally oblate spherical shapedstructure whose outer “skin” defines a material reservoir or pocket1010. The reservoir 1010 is bounded by a thin, flexible material surfaceor skin 1013 that encloses an interior volume 1015 for retainingsubstances that maintain the construct in the active profile. In onesuch variation, the reservoir 1010 contains a filler material 1200,which may be a liquid or a semi-solid or gel-like material. In general,the volume of filler material 1200 is initially low, that is, whenconstruct 1000 is in its initial, pre-deployment condition. The volumeof filler material 1200 increases after the construct's deployment.Construct 1000 in FIG. 2 illustrates the fully expanded or active statebut for clarity only a representative portion of filler material 1200 isshown.

The transition from initial, unexpanded state construct 1000 to theactive state can be effected by increasing the volume of filler material1200 enclosed in reservoir 1010. Additionally, the volume can beexpanded through expansion and/or swelling of the filler materialalready inside the reservoir 1010. For example, as was described incommonly assigned U.S. patent application publication numberUS2011/0295299, one exemplary embodiment filler material 1200 in theinitial state is a pre-determined volume of dry hydrogel granules. Thedry hydrogel granules can swell, for example, between 10 and 400 timestheir dry volume when exposed to an appropriate liquid, generally anaqueous solution.

In the variation shown in FIG. 2, once a medical practitioner or userdeploys of the construct 1000 into the stomach, the aqueous liquid inthe stomach migrates into the reservoir 1010 and creates a slurry ofliquid and substantially fully hydrated hydrogel. As is well known,hydrogels absorb water from their surroundings causing swelling of thehydrogel. In the embodiment of FIG. 2, the volume of dry hydrogel ispre-selected to have a fully swollen, unconstrained volume that slightlyexceeds the volume of the reservoir 1010. Under constraint, hydrogelscannot swell to a greater volume than the limits of the constrainingvolume; however, constrained hydrogels can and do exert pressure againstthe constraint. Thus, reservoir 1010 becomes a structurallyself-supporting structure, when filled with an excess of swollenhydrogel (that is, when the unconstrained volume of the swollen hydrogelis greater than enclosed interior volume 1015). In other embodiments,reservoir 1010 is filled and pressurized with other filler. In itsexpanded state, reservoir 1010 can be sufficiently elastic to deformunder external pressure and returns to its pre-deformation shape whenthe pressure is removed. In yet additional variations, the fillermaterial can be selected such that it hardens after a period of time tobecome its own skeletal structure or to support the skin. Such a fillercan be selected to eventually degrade based on the environment in thestomach or digestive tract.

Assemblies 1000 under the present disclosure can comprise a materialsurface or skin 1013 that is substantially impermeable to liquids and/orgases. In these embodiments, filler material 1200 can be, respectively,a liquid or a gas. Additionally, filler material 1200 can be afluid-swellable material such as hydrogel, which, when hydrated, becomesa solid, semisolid or fluid-like gel or slurry. As illustrated in FIG.2, embodiments comprising a substantially impermeable skin 1010 furthercomprise a fluid transport member 1100 that allows for the migration offluid through the skin. In some examples, as noted above, the fluidtransport member includes a sealable fluid path that may or may not becoupled to an additional fluid conduit. In additional variations, thefluid transport member can include a localized liquid transfer member1100 that is disposed in an orifice 1020 through the skin 1013 andfacilitates the migration of fluid between the interior and exterior ofreservoir 1010. One such example can be found in U.S. Provisionalapplication entitled “Resorbable Degradation System” Ser. No. 61/723,794filed on Nov. 8, 2012, the entirety of which is incorporated byreference herein

As noted above, in certain variations, where the device assembly 1000comprises a substantially fluid impermeable material surface, aconstruct 1000 in the expanded active profile can remain in stomach orother portion of the body indefinitely until released. Therefore, asnoted above, devices of the present disclosure can include a releasematerial 1400, which allow the construct 1000 to reduce in size from theactive profile and ultimately pass through the body. Such an activerelease material 1400 configuration allows for on-demand release of theconstruct. As noted above, once activated, degraded, or otherwise madeunstable, the release material allows migration of filler material fromthe reservoir and device assembly. In some variations, activation of therelease material opens a passage in the skin 1013 of the device 1000.Alternatively, or in combination, activation of the release material canresult in reduction of the integrity of the skin forming the barrierabout the reservoir. Once the barrier is compromised, the fillermaterial can safely pass into the body. Regardless of the means, theactivation of the release material and release of the filler materialcollapses the device 1000 leading to egress or removal of the device1000 through the body (in this variation through the lowergastro-intestinal track). As noted above, variations of the devicesdescribed herein include a release material that is activated byexposure to an exogenous substance.

In certain variations, the device assembly 1000, in the active profile,comprises a highly oblate spheroid wherein the skin 1013 can be a thin,film-like material that is soft, tear-resistant, flexible, substantiallyinelastic, and non-self adhesive. Such features can be beneficial for adevice that is to be compressed into a small oral dosage form foradministration. In certain examples, the skin 1013 comprised a 0.0015inch thick polyether polyurethane film. In a simple variation, an oblatespheroid can be created from skins forming an upper material surface anda lower material surface, wherein upper material surface and lowermaterial surface are sealed to each other as shown by seam 1004 in FIG.2. One such means for sealing the device 1000 comprises an ultrasonicweld around the periphery of adjoining materials. As will be describedin more detail below, in a possible assembly method, the upper and lowermaterial surfaces are formed as nominally identical, substantiallydisk-like shapes of material, welded in a band around most of theircircumferences, the assembly is then inverted (turned inside out)through an unwelded section. Once the assembly is inverted, the weldedmaterial forms the seam 1004 that projects.

FIGS. 3A to 3E illustrate additional variations of device assemblies 100having various active profiles. It is understood that the shapes shownin the illustrations disclosed herein are examples of possiblevariations of the device. FIG. 3A illustrates a device 100 having adonut shape (i.e., an oblate shape with an opening 103 in or near acenter of the device assembly 100). FIG. 3B illustrates a deviceassembly 100 having a rectangular or square-like shape. FIG. 3Cillustrates a triangular shaped device assembly 100. Again, theillustrated variation includes an optional opening 103. Some variationscan have a contiguous surface, while others can incorporate one or moreopenings 103 as shown. FIG. 3D illustrates a device assembly 100 havinga shape that comprises a plurality of protrusions 132 that form thedevice assembly 100. The number and direction of the protrusions canvary from that shown. FIG. 3E shows a variation of a device assembly 100having a crescent shape.

The devices shown in FIGS. 3A to 3E also show release materials 106,whether located on an interior of an opening 103 or on an exterior ofthe shape. The variations shown in FIG. 3A to 3E can also include theadditional features of the device assemblies described herein.

Alternatively, the release material can comprise a filament, clip, band,cap, or other structure that mechanically closes the edges of the skin.Further, as described below, a source of stored energy, such as a loadedspring or compressed sponge or other material, may be included in therelease assembly, where such kinetic energy is also released uponactivation of the release material and which may improve the performanceof such assembly.

FIG. 4 illustrates a variation of a fluid transfer member 1100 alsohaving a sealable fluid path 1110 for use with the device assembliesdescribed herein. In this example the fluid transfer member 1100 alsoincludes an elongate fluid conduit, or tube, that passes through atunnel valve that functions as a sealable fluid path 1110. The tunnelvalve 1110 can be positioned in an orifice in the upper 1014 or lower1016 material surfaces or in an opening in a seam 1004 of the deviceassembly. This variation of the tunnel valve 1110 comprises an elongateportion 1022 that extends within the reservoir of the device assembly.In some variations, the tunnel valve can extend beyond the seam 1004 orbeyond the exterior surface of the device assembly as discussed above.

As illustrated in FIG. 4, portion of the fluid transport member includesa tunnel valve 1110 that can comprise two layers forming an orifice1020. The orifice 1020 forms a fluid path that allows a remainder of thefluid transport member 1100 to deliver fluids into the reservoir. Inthis variation the fluid transport member 1100 further comprises aconduit. However, as noted herein, the fluid transport member cancomprise a wick type device or any fluid source that allows delivery offluids into the reservoir of the device. As also noted herein, avariation of the device permits a portion of the fluid transport member1100 to be detachable from the tunnel valve 1110 where detachmentpermits the tunnel valve 1110 to prevent egress of fluids or othersubstances from within the reservoir. Sealing of the tunnel valve 1110can occur via a rise in pressure within the reservoir. Alternatively, orin combination, a number of other mechanisms can result in sealing orclosure of the orifice 1020 in the tunnel valve 1110. For example, inadditional variations the surfaces forming the orifice 1020 can sealupon contact or the length of the tunnel valve 1110 combined with itsflexible nature can simply make it difficult for substances, such as anexpanded hydrogel, to travel through the elongated portion 1022 of thetunnel valve.

FIG. 4 also shows the conduit 1100 extending through the tunnel valve1110 such that it extends into the reservoir. However, in alternatevariations, the device end of conduit 1100 can remain within an interiorof the orifice 1020 of the tunnel valve 1110.

In one variation of the tunnel valve 1110, as illustrated in FIG. 5, thetunnel valve 1110 shaped roughly as the capital letter T, wherein thevertical stem of the T comprises the elongate passage 1022 and whereinthe crossbar of the T, in part, forms an increased attachment surfacethat can be attached to the skin as noted above. As may be seen in FIG.5, tunnel valve 1110 can be disposed through an opening in the seam1004.

Some examples of materials used to form a tunnel valve include thin,film-like materials. For example, variations include tunnel valvematerials that have properties similar to the material used in materialsurface or skin of the device. Additional materials include but are notlimited to polyurethane, nylon-12, and polyethylene. Such layers can bebetween 0.001″ and 0.1″ thick. In one example a tunnel valve included athickness of 0.0015″

As discussed above, variations of a device assembly include a releasematerial that is coupled to a portion of the skin to form a barrier toretain substances within a reservoir of the device. FIG. 6A illustratesa partial view of a variation of an invaginated section 126 of a skin102 of a device assembly 100. As discussed herein, the skin 102 caninclude an first surface 122 and second surface 124 joined at a seam118. The seam 118 can include any number of unjoined sections that areintended to function as release areas 128. In the illustrated example,the release area 128 is bounded by an invaginated section 126 of theskin 102. The invaginated section 126 of the skin can comprise a tuck,fold, pucker, bulge, extension, etc. in the skin 102. Alternatively orin addition, the invaginated section 126 can be formed within a first122 or second 124 surface of the skin 102 rather than within a seam 118.

The release area 128 of the invaginated section 126 ordinarily forms apassage that is fluidly sealed by a release material 106. The releasematerial can comprise a mechanical closure (such as a staple-typestructure or a filament that ties together the invaginated structure).Alternatively, or in combination, the release material 106 can comprisea temporary seal or other joining of the edges of the invaginatedsection 126. In additional variations, the release material can extendoutwardly from an exterior surface of the skin. In some variations, therelease material 106 is disposed on the invaginated portion 126sufficiently close to the skin to be affected by a temperature increasecaused by delivery of the exogenous substance.

Other variations of a device assembly 100 include an energy storageelement that encourages a rapid and more complete opening of the releasearea 128. FIG. 6B illustrates a partial view of the interior of a deviceassembly 100 comprising an invaginated section 126 of the skin 102. Aswas discussed in relation to the variation of FIG. 6A, the releasematerial 106 in this variation forms a temporary seal by tying off theinvaginated section 126. In this variation, an energy storage element127 is disposed within the invaginated section 126 of the release area128 and is further disposed to be within the region tied off with therelease material 106.

Energy storage element 127 is, generally, a compressible elasticmaterial, for example a latex foam. In some variations energy storageelement 127 is generally cylindrical with a diameter at leastfractionally smaller than the diameter of the invaginated section 126.As shown in FIG. 6A, when device 100 is deployed in the body, releasematerial 106 is tied firmly around the invaginated section 126 at theposition of the energy storage element, thereby simultaneously sealingthe invagination and compressing the energy storage element. Thiscompression of the elastic material in the energy storage element 127generates a tension in the release material tied around the invaginatedsection 126 that is greater than the tension in the release material tieused to seal an invagination alone.

FIG. 6C illustrates the invagination section 126 after an exogenoustrigger has been used to activate the release material 106. Asillustrated in the figure, the release material is broken apart inseveral small segments, allowing the invaginated section 126 to open andrelease the filler material, not illustrated for clarity. The increasedtension generated by the energy storage element encourages the releasematerial to break apart sooner, more rapidly and more completely than itotherwise would.

Examples of the release material can include poly(caprolactone) or PCL.In such variations, PCL softens, melts, and weakens above apre-determined temperature. In some cases the pre-determined temperatureis greater than normal body temperature. Accordingly, in suchvariations, the exogenous substance can comprise a heated fluid that canraise the temperature of the PCL without causing injury to the adjacentareas of the body. As the PCL release material degrades, the structuralintegrity of the joined region of the release section (such as theinvaginated section 126) decreases. In one example, the release materialis a modified PCL, wherein the modification comprises lowering themelting point of unmodified PCL from its normal melting temperature to ahuman-tolerable temperature.

For example, an on-demand degrading construct composed of nylon-12 canbe constructed by first fabricating a 1″ circular annulus of 1.5 milPollethane, also known as 55DE Lubrizol 2363 polyether polyurethane(available from Specialty Extrusions Inc. of Royersford, Pa., USA). Acircular degradable patch of poly(caprolactone) (PCL) (with a meltingpoint, T_(m), equal to ˜47° C.; available from Zeus Industrial Productsof Charleston, S.C., USA) can be RF-welded to the Pellethane annulus,covering the hole, creating a T_(m)-modified PCL patch surrounded by arim of Pollethane. The Pollethane rim can then be RF-welded to a sheetof nylon-12, which can then be used for further construction.

Examples of release materials can include biocompatible manufacturedpolymers. Table 1 is a compilation of some pertinent properties ofseveral biocompatible materials that can be extruded or otherwisemanufactured in filamentary form and which also can be degraded. Some ofthese materials, poly(vinyl alcohol) are stable in dry environments butdissolve very quickly in moist environments. Other materials eitherdissolve quickly in caustic solutions (e.g. extremely alkaline) or meltquickly at high temperatures, but these conditions all exceed those thatcan be tolerated by humans. Some biocompatible polymers, for exampleco-polymers of methacrylic acid and methyl-methacrylate, dissolve inliquids having physiologically relevant pHs. For example, they remainstable at pH<7.0 but dissolve at pH>7.0.

Degradation Degradation Degradation Polymer Type Mode Condition TimePoly(glycolic acid) Bioabsorbable Gradual Exposure to water 2-3 monthshydrolysis or acid Poly(dioxanone) Bioabsorbable Gradual Exposure towater 6-8 months hydrolysis or acid Poly(lactic-co- BioabsorbableGradual Exposure to water 2 months glycolic acid) hydrolysis or acidPoly(vinyl alcohol) Bioabsorbable Rapid dissolution Exposure to anySeconds aqueous solution Methyacrylic acid Bioabsorbable Hydrolysis;Exposure to Days at near methyl-methacrylate on-demand alkaline pHneutral pH and co-polymers pH-dependent minutes to hours dissolution atalkaline pH Poly(caprolactone) Bioabsorbable Hydrolysis; Exposure toheat 6 months at on-demand at temperatures less temperatures thanmelting point, greater than 60° C. seconds at or above melting pointPolyester Non- None None N/A bioabsorbable Poly(propylene) Non- NoneNone N/A bioabsorbable Nylon Non- None None N/A bioabsorbable

As the release section opens the reservoir to the surroundingenvironment the opening provides an open path out of the deviceassembly. The open path allows the contents of the device assembly, suchas the filler material, to become exposed to the gastric contents andfreely to exit reservoir. When positioned within the stomach, normalgastric churning assists in emptying the contents of the device assemblyallowing for the entire device along with its contents to pass from thebody. In some variations, the membrane that forms the skin will providelittle or no structural support. This configuration allows the body'snatural squeezing strength to be sufficient to extrude any reasonablyviscous substance out of the device assembly.

FIG. 6D provides a schematic illustration of another example of a deviceassembly 100 having a release material 106 located on a surface of theskin 102. One example of such a release material comprises a degradablepatch 106 that, when degraded, opens the physical barrier surroundingthe reservoir 104 to allow filler material 108 (swollen or unswollen) toexit the device assembly 100. The device assembly 100 comprises a skinmaterial to which release material 106 can be joined (e.g. by heatsealing, RF-welding, impulse heating, or any other means). In certainvariations, the release material/degradable patch 106 comprises amaterial or combination of materials that remains impermeable to waterand hydrogel after deployment and can be degraded “on-demand” inresponse to an exogenous substance or in response to a condition createdwithin the body being the result of the administration of the exogenoussubstance.

In one example, the release material can range from 25 microns thick; upto 2.5 millimeters thick. In another example, release material is amodified poly(caprolactone) with melting point T_(M)=47° C. (availablefrom Zeus Industrial Products of Orangeburg, S.C. USA). In additionalembodiments, degradable patch 106 may be poly(glycolic acid) orpoly(L-lactide acid) (available from Poly-Med, Inc of Anderson, S.C.).

FIGS. 7A and 7B show one example of an exploded, assembly view of adevice assembly 100 (where a fluid transport member is omitted for thesake of clarity). As shown, the device assembly 100 can include amaterial skin comprising two layers of material that form an upper skin122 and a lower skin 124. As noted herein, the layers can be joined toform a seam. Clearly, the presence of a seam is optional and somevariations of devices under the present disclosure will not include aseam or will have similar types of joined regions of material topreserve the skin as a physical boundary for the contents of thereservoir. Again, the device assembly 100 is shown in the shape thateventually assumes an oblate spheroid shape. However, other shapes arewithin the scope of this disclosure. In one variation, the skincomprises substantially inelastic materials 122 and 124 that are joinedaround a perimeter leaving openings as discussed herein. It will beunderstood that, the shape of the device referred to as an oblatespheroid for descriptive purposes. In other embodiments wherein one ormore devices may be joined to comprise a multi-bodied assembly, eachindividual device can be assembled from one or more sheets of film-likematerial that are cut to a pre-designed shape. FIG. 7A shows the device100 in an inside-out configuration in mid-assembly. As shown, theinvaginated portion 126 can be secured with a filament release material106 and/or a sealing release material 106 located within a release area128. FIG. 7B illustrates an exploded view of the construct of FIG. 7Aafter the structure is inverted and a filler material is inserted into areservoir formed by the skin materials 122 and 124.

Material Surface or Skin

The type of material or skin will depend upon the intended application.In some variations, a skin will be chosen as a balance of selecting asufficiently thick film-like material that has adequate strength. Forexample in some variations, tear resistance can be preferred to enablethe finished construct to be compression into as low a volume capsule aspossible. The inventors have determined that thin films with a thicknessranging from 0.5 mils to 4 mils are generally suitable. However, thedevices described herein can comprise a greater range of thicknessesdepending upon the particular application, including a range ofthicknesses in different parts of the same construct. In someembodiments, the film-like material must be weldable or adherable toother materials such as might be used in valves 1110, filler materialrelease mechanisms 1400, and/or attachment interfaces as describedherein.

In additional embodiments, the film-like material exhibits lowtransmission rate of filler material, both before and after deviceexpansion. In some embodiment the film-like material exhibits a lowmoisture vapor transmission rate. Additionally, some film-like materialalso exhibits high chemical resistance to the variable conditionsencountered in the stomach. These conditions include low pH, high salt,high detergent concentrations (often in the form of bile salt reflux),enzymatic activities (such as pepsin), and the variable chemistries ofchyme that depend upon the nature and content of consumed food. Forthose devices used in the gastric space, the material must also becomprised of biocompatible materials that can safely be in contact withthe gastric mucosa for the duration of the treatment course.

The devices described herein can use numerous thermoplastic elastomers,thermoplastic olefins and thermoplastic urethanes that can be extrudedor cast into single-layer or multi-layer films which are suitable forembodiments of the gastric device. Example base resins that may beemployed include polypropylene, high-density polyethylene, low densitypolyethylene, linear low density polyethylene, polyester, polyamide,polyether polyurethane, polyester polyurethane, polycarbonatepolyurethane, bi-axially oriented polypropylene, Polyvinylidenechloride, ethylene vinyl alcohol copolymer, and Ethyl Vinyl acetate.Some embodiments comprise single layer films whilst other embodimentscomprise multiple layer films. Other embodiments consist of multilayerfilms including one or more tie layers to prevent layer separation.

In some embodiments, the film-like material may be coated with othermaterials. For example, in some embodiments hyaluronic acid coatings canbe employed to improve softness and lubriciousness. In otherembodiments, coatings such as Parylene® can be applied to improve thechemical resistance of the gastric mucosa-exposed film surface. In someembodiments, wax coatings, PVDC coatings, vacuum-metallization, orParylene® coatings may be applied to the surface of the film to reduceits moisture vapor transmission rate.

In one example, the film-like material used comprised a 1.5 milpolyether polyurethane film. In other embodiments the film-like materialis a 1 mil nylon 12 film or a 1.5 mil LLDPE film. In another example,the film-like material consisted of a multi-layered structure comprisingan outer layer of polyurethane, a middle layer of PVDC or EVOH, and aninner layer of polyurethane.

Filler Material

Generally, a filler material that has a high swelling capacity andachieves a semi-solid consistency is useful to enable the finishedconstruct to be compressed into as low a volume initial state aspossible but still maintain rigidity once expanded. However, unlessspecifically noted, variations of the device can employ a number ofdifferent types or combinations of filler materials. During variousexperiments, it was determined that superabsorbent hydrogel polymerswith a mass:mass swelling capacity of between 100 and 1000 are generallysuitable, where a mass:mass swelling capacity of 100 is defined hereinto mean that 1.0 g of dry hydrogel will absorb water and swell to becomea semi-solid mass of 100.0 g.

Typically, suitable hydrogels swell maximally in the presence ofdistilled water and a number of these hydrogels also de-swell (releasesbound water) in the presence of the variable environmental parametersencountered in the stomach. For instance, parameters such as pH, saltconcentration, concentrations of emulsifying agents (often in the formof bile salt reflux), enzymatic activities (such as pepsin), and thevariable chime chemistries, which depend upon the nature and content ofconsumed food can affect the swelling/deswelling behavior of certainhydrogels. Typical hydrogel swelling times range from between 5 minutesand 1 hour. In one variation, the hydrogel fully swells in under 15minutes and fully de-swells in less than 10 minutes after exposure incertain environments. Many hydrogels are supplied with particle sizesdistributed between 1 and 850 microns. In certain variations, gastricapplications benefit from the use of hydrogel particle sizes distributedbetween 1 and 100 microns. In addition, the hydrogel must also becomprised of biocompatible materials that can be safely in contact withand excreted by the gastrointestinal tract. Examples of suchbiocompatible superabsorbent hydrogel polymers that possess swellingcapacities, swelling times, and de-swelling times suitable forembodiments of gastric construct include poly(acrylic acid),poly(acrylamide), or co-polymers of poly(acrylic acid) andpoly(acrylamide). Another such material that can be used as a fillermaterial is a crosslinked poly(acrylic acid) with particle sizedistribution ranging from 1-850 microns and swelling capacity of 400.

Shapes

As discussed above, certain variations of the device approximate ahighly-oblate spheroid comprising a diameter in the X-Y plane and athickness along the Z-axis as illustrated in FIG. 2. In certainvariations, the expanded dimensions of the device assembly can rangefrom having a diameter between 2 inches and 10 inches. In anotherembodiment, the diameter of the construct is approximately 4.6 inches.The Z-axis thickness can range between 2 inches and 5 inches. However,the device assembly, unless otherwise claimed, is not limited to anyparticular dimension. The data below of construct parameters providesthe experimentally determined dimensions of two constructs having theoblate spheroidal shape.

Parameter Construct 1 Construct 2 Unexpanded diameter (inches) 4.7 5.8′Maximum swollen volume 300 ml 500 ml Expanded diameter (inches) 3.644.63 Expanded thickness (inches) 2.40 2.46

Liquid Transfer Valves

FIG. 8A shows an additional variation of a portion of a device assembly,in other embodiments liquid transfer member comprises a valve 150,wherein valve 150 is disposed in orifice 148 and provides a control overthe fluid permeable path through otherwise impermeable material surface102. In some embodiments valve 150 comprises a multilayer materialstructure composed of regions of permeability 152 juxtaposed againstregions of impermeability 154, whereby fluid may transmigrate betweenthe exterior and the interior of reservoir when the regions ofpermeability 152 and impermeability 154 are not pressed together intight juxtaposition and whereby fluid is inhibited from transmigratingwhen the regions 152, 154 are pressed together tightly. In someembodiments valve 150 is self-closing. That is, valve 150 changes fromallowing fluid transmigration to inhibiting fluid transmigration withoutexternal activation. In one embodiment valve 150 self-closes in responseto the increasing pressure of the expanding filler material orincreasing pressure within the reservoir, for example, swelling hydrogelpressing the regions 152, 154 sufficiently close together to form abarrier.

As noted above, the device assemblies described herein can include awick-type structure that serves as a source to deliver fluids into thereservoir. One example of such a wick includes a filamentary materialcapable of conducting a liquid from one end to the other by capillaryaction. The wick can be used in a stand-alone manner or with a selfclosing valve.

In yet other embodiments liquid transfer mechanism 1100 comprises amechanical valve. Mechanical valves of suitably small dimensions,comprising biocompatible materials, are well known in the art and arecommercially available. A mechanical valve that serves as liquidtransfer mechanism 1100 comprises a one-way or “check” valve designwhich allows fluid to enter reservoir 1010 but prevents fluid fromexiting the reservoir. Alternatively, a mechanical valve that serves asliquid transfer mechanism 1100 may have a normally open state but whichself-closes when internal fluid pressure is greater than external fluidpressure.

FIG. 9A shows another aspect of devices as described herein, forexample, construct 200 can comprise one or more fluid transport members208. As discussed herein, the liquid supply sources 208 are configuredto allow fluid to enter the reservoir to combine with a filler material202 disposed in an unexpanded device assembly 200. In some variations,the fluid transport member 208 can be coupled to a valve 210 thatreduces, blocks or stops transport of liquid when filler material 202 issubstantially hydrated as shown in FIG. 9B. Such a shut off ability isbeneficial as it reduces the likelihood of filler material 202 becomingcontaminated by gastric contents when the device assembly is in theactive profile. Examples of such shutoff-mechanisms are describedherein. FIGS. 9A and 9B also illustrate variations of the deviceassemblies 200 as including a tether 214 or other delivery systemcoupled to an attachment interface 216. FIG. 9A also illustrates twoareas on the skin of the device having sections of release materials206. As noted herein, the release material is responsive to an exogenoussubstance that causes degradation, melting, and/or other instability ofthe release material to allow exposure of the reservoir to the body.This allows the contents of the reservoir to pass from the device andeventually allows for the device to pass from the body.

FIGS. 9A and 9B also illustrate a device 200 having a delivery system214, 216 attached thereto. The delivery system 214, 216 can comprise afilamentary tether 214 that is, generally, attached to the body of thedevice 200 via an interface 216. The attachment interface 216 can bedesigned as a structurally inherent part of the delivery system (i.e.,it cannot be removed from the device body as a separate, stand-aloneitem). Alternatively, the interface 216 can be designed as an elementthat is added on to device 200.

Valves

FIGS. 10A and 10B illustrate one example of a valve driven by expansionof filler material 234 within a reservoir 236 of the device assembly230. The valve 232 is positioned or otherwise disposed in an orifice 238in the material surface or skin 232. This permits fluid to flow into orout of the reservoir 236 when the valve 232 is in an open configuration.In some variations, the orifice 238 comprises, typically, a smallpercentage of the total surface area of material surface 228. Materialsurface 228 is generally impervious or of limited permeability to thefluids in which device 230 is typically immersed. Orifice 238 can be anopening in the otherwise fluid-tight barrier formed by the skin 232.

FIG. 10A also illustrates a pre-determined amount of filler material 234within the reservoir 236. In some variations, the pre-determined amountis generally measured by dry mass. The dry mass of filler material 234is determined by the amount of filler material 234 needed to fill theknown volume of the expanded device 230 when the filler material isfully hydrated. When expanded, the filler material applies a pressurewithin the reservoir 236, which provides a shape-restoring force thatresists externally applied deforming forces.

FIG. 10A also shows valve 232 covering the orifice 238. This variationof the valve 232 includes one or more flow control layers 240 that aidin closing of the valve upon action by the filler material 234. FIG. 10Billustrates expansion of the filler material 234, which increasespressure against the valve 232 and closes the fluid path by compressingthe flow control layers 240

Turning back to FIG. 10A, before filler material 234 expands, valve 232is fully open; that is, it allows fluid to pass through the valve ineither an inward or outward direction. On the other hand, after fillermaterial 234 expands, typically via hydration, the valve 232 fullycloses, as shown in FIG. 10B.

In some embodiments valve 232 comprises a filler material containmentlayer 242. Generally, containment layer 242 is at least partly fluidpermeable and simultaneously able to contain filler material 234, in itsdry or its hydrated state, within construct 230. In some embodimentsfiller material containment layer 242 is also a flow control layer; thatis, a single layer in valve 230 can simultaneously be a part of the flowcontrol function of valve 232 and perform the filler containmentfunction of containment layer 240.

FIGS. 10C and 10D show another variation of a valve 232. In this examplethe valve 232 comprises more than one layer. As shown, this hybrid valve232 comprises two demilunar flow control layers 248, each of the layershaving a hybrid construction being permeable in some generallysemi-circular (viz., demilunar) regions 250 and impermeable in otherregions 252. The impermeable regions 252 of one layer are at leastcomplementary to the permeable regions of the second layer; that is,where one layer has a permeable region the other layer has animpermeable region; generally there will be regions in which both layersare impermeable. Examples of the materials include a permeable patchcomprising a polyester mesh and an impermeable semicircular patchcomprising latex.

As illustrated in FIG. 10D, hybrid valve 232 comprises two substantiallyidentical demilunar hybrid flow control layers, one on top of the other,wherein the two layers are oriented so that impermeable region 252 of afirst hybrid control layer is aligned with the fluid permeable region250 of a second hybrid flow control layer. By symmetry, impermeableregion 252 of second hybrid flow control layer is aligned with the fluidpermeable region 250 of first hybrid flow control layer. The two layersare affixed, typically with glue, around their periphery only, therebyallowing the central areas of the two layers to move apart freely.

It will be obvious to one of ordinary skill in the art that the circularshape of exemplary hybrid valve is a design choice made primarily tosimplify alignment during assembly and installation. The principle ofoperation of a hybrid valve—that the two flow control layers havecomplementary permeable and impermeable regions—is independent of theperipheral shape of the valve or the orifice to which the valve shapeand size is matched. For example, another exemplary hybrid valve isillustrated in FIG. 10E wherein each hybrid flow control layer 248 isgenerally rectangular and the impermeable region 252 and permeableregion 250 are triangular.

Furthermore, permeable region 250 and impermeable region 252 in anyindividual flow control layer need not have identical shapes. Forexample, as shown in FIG. 10F, which shows an exploded view of a valveassembly, a permeable region in one individual flow control layer maybe, for example, a circular region, and the impermeable region may be anannulus disposed around the circular permeable region. However the twolayers of any one hybrid valve must at least have complementarypermeable and impermeable regions; that is, when the two layers areoverlaid there is no permeable area in communication with the exteriorof the device.

In these exemplary embodiments of a hybrid valve, the flow control layerdisposed on the internal side of the valve preferably can also functionas filler material containment layer, with containment being achieved bythe mesh comprising permeable patch. Alternatively, a separate innermostfiller material containment layer must be added to the assembly.

In other embodiments, hybrid flow control layer is fabricated by joininga patch of permeable material and a patch of impermeable edge-to-edge,wherein the joint may be a butt joint, for example, or a lap joint, fora second example, wherein further the outer periphery of the edge-joinedmaterials is designed to fill or cover orifice. In another exemplaryembodiment of a hybrid valve the skin itself can serve as one of theflow control layers.

Wick Permutations

FIG. 11A illustrates another variation of a device 300 having a fluidtransport member that comprises a fluid wick 302 that extends into areservoir 304 of the device 300. Typically, a fluid wick structureconveys fluids from a wet end to a dry (or “drier”) end by capillaryaction. For example, if one end of liquid wick structure 302 is immersedin a liquid whilst the other end of liquid wick structure 302 isdisposed in air, then the liquid moves through the wick structure 302from the immersed end to the “in-air” end, at which end, typically, itwill be absorbed by a filler material. The liquid will continue to flowthrough the liquid wick structure until such time that the “in-air” endis also immersed in liquid (that is, typically, immersed in a puddle ofaccumulated fluid).

Liquid wick structure 302 can optionally comprises a strip or thread ofwater absorbent material, for example, an absorbent matrix of cottonpulp (e.g. as in a sanitary napkin), polyvinyl acetal (e.g., as in aneye wick), polyvinyl alcohol sponge (e.g., as in ear wicks), or othermaterials typically used in, for example, surgical sponges.Alternatively, liquid wick structure 302 can comprise a strip ormulti-strand thread of non-water-absorbing material, for examplecapillary-channeled nylon or polyester, wherein small capillaries areformed between the interior walls of the non-absorbent material. Thewick can also comprise oxidized cellulose (available from Jinan VincentMedical Products Co., Ltd, 122#East Toutuo Street Huangyan, Jinan,Shandong, China). Oxidized cellulose is known to absorb water but, as itis a polysaccharide, eventually solubilize after prolonged immersion inwater.

In one variation, a wick structure 302 can have a substantially circularcross-section, the cross-section generally being greater than 2 mm indiameter and less than 8 mm in diameter, although both greater andsmaller diameter wicks may be appropriate for large or small constructsrespectively, the limits being determined by practicality andconvenience rather than functionality.

Wick structure 302 is designed to convey fluid from the exterior to theinterior of device 300, through an orifice in material surface 306; itslength is preferably the sum of a convenient exterior segment, perhaps 2cm, and an interior segment SKG2100 that is long enough to reach fromorifice 308 to the furthest interior space in which filler material maybe disposed. For some variations of the device, an interior segment ofthe wick 302 is approximately 6 cm, so a typical liquid wick structure302 can be up to approximately 8 cm long. In other embodiments liquidwick structure 302 is between 4 cm and 12 cm in length. However, anyrange of wick length is within the scope of this disclosure.

In one variation, liquid wick structure 302 is inserted through anorifice 308 in device 300, where the device 300 is otherwise impermeableto fluid. Orifice 308 can be designed with a diameter that isapproximately 50% of the diameter of liquid wick structure 302 to ensurethat liquid wick structure 302 fits tightly and securely into orifice308 when liquid wick structure 302 is dry. In some embodiments, orifice308 may also have a diameter that is less than 50% of the diameter ofliquid wick structure 302. The minimum diameter for orifice 308 islimited by constriction of the capillary action in liquid wick structure302. That is, depending on the internal structure of liquid wickstructure 302 and its material properties, too small an orifice willsubstantially shut off the transmigration of fluid through the liquidwick structure.

Alternatively, in some embodiments, orifice 308 may have a diameter thatis greater than 50% of the liquid wick structure diameter, particularlyif liquid wick structure 302 is being securely held by other means. Witha large (greater than 50% orifice of the liquid wick structurediameter), liquid wick structure 302 can be heat-sealed, glued, orotherwise affixed in place in orifice 308 to prevent it from beingdisplaced from its operational disposition.

As illustrated in FIG. 11B, when the construct, or at least the exteriorsegment of liquid wick structure 302 is immersed in a liquid, liquid isinitially drawn into the absorbent wick material of liquid wickstructure 302 and is further drawn from the wet wick material toward thedry wick material until interior segment of liquid wick structure 302 issubstantially saturated. Liquid, on reaching the surface of liquid wickstructure 302 (and in particular the end of interior segment), can beshed by dripping or it may be drawn off by contact with the absorbent,dry filler material. Filler material 306 swells as it absorbs liquid.The pre-determined quantity of dry filler material, when fully expanded,fills the construct to a slightly positive pressure and surroundsinterior segment in a hydrated mass 234. This mass is the functionalequivalent of a liquid bath. With both ends of liquid wick structure 302are immersed in fluid, the liquid wick structure's capillary actionstops or slows considerably, thereby ending fluid movement between theexterior and the interior of construct 300.

As illustrated in FIG. 12A, some exemplary embodiments of liquid wickstructure 302 is fluidly coupled to a secondary, interior bag, pouch, orother container 310 to ensure that interior segment of the wick 302 isin direct contact with filler material 234 located within the container310.

As filler material 234 swells, the container 310 releases fillermaterial 234 into the reservoir of the device 300, where it continues toreceive hydration from liquid wick structure 302. In one embodiment,illustrated in FIG. 12A, secondary bag 310 is water soluble, dissolvingquickly as the partially hydrated hydrogel swells within it. In otherembodiments secondary bag 310 comprises one or more weakened seams, theweakened seams splitting open as the hydrogel swells against it. In yetother embodiments, the entire secondary bag 310 comprises a structurallyweak, permeable material, unable to contain the pressure of the swellinghydrogel. In yet other embodiments, secondary bag 310 comprises seamsclosed with sutures, the sutures being either inherently weak or watersoluble. Any portion of a wick can be coupled to a container, not justthe ends of the wick. For example, a wick can be folded such that thefolded end is positioned within the container.

The wick 302 can be held in place within the container 310 as describedabove for the orifice. Alternatively it may be sealed closed byheat-sealing, gluing, or other means so that the tip of interior segmentis disposed in direct contact with filler material 234.

In some embodiments, liquid wick structure 302 may be fabricated from amaterial that dissolves or degrades in liquid comparatively slowlyrelative to the time it takes for the filler material to fully expand.The material selected for this embodiment maintains its integrity andwicking ability long enough to fully hydrate filler material 234 butthen degrades and disappears once the filler material is fully expanded.Examples of such materials include thin, cellulose-derived, porous wovenor nonwoven materials and ‘ropes’ made of smaller tubes, includingcombinations of nanotubes.

FIG. 12B illustrates another embodiment of a device 300 having multipleliquid wick structures. This embodiment comprises a dual wick structurein which a single wick structure 302 delivers fluid into the reservoirthrough both ends. As shown, a wick is threaded through both sides ofthe skin of the device so that the wick is exposed on both sides. Thesetwo exterior wick segments absorb fluid and convey the fluid between anexterior of the device and the reservoir. Clearly, two or more wickstructures can be used rather than both ends of a single wick structure.

As shown in FIG. 12C, in other embodiments the interior segment of asingle liquid wick structure 302 is divided into two or moresub-segments. Sub-segments of the wick structure 302 can be directed todifferent locations in the reservoir of the device to distributehydration fluid 1105 more efficiently or, as discussed above, each endcan be directed to a secondary container.

In another aspect, a wick structure 302 can be affixed to a portion ofthe interior of the reservoir as illustrated in FIG. 12D. As shownabove, the wick initially extends outside of the device. Upon swellingof the filler material, as the device expands, the section of the wickthat is initially outside the device is pulled into the interior of thedevice assembly because it is affixed or secured to the interior of thereservoir.

Clearly, variations of the wick structure can be combined with otheraspects and features described herein. Moreover, any embodimentdisclosed herein can be combined with aspects of alternate embodimentsor with the embodiment itself. For example, the wicks described hereincan be combined with the valve mechanisms described herein and/or can becombined with the release materials discussed throughout thisspecification.

FIG. 13A illustrates a variation of a tunnel valve as discussed above.As shown, the tunnel valve forms a sealable fluid path that preventsmaterial from escaping from the interior of the device. FIG. 13Aillustrates an example of a device with a tunnel valve forming thesealable fluid path. As shown, device assembly 326 contains a valvemember 330 comprising a fluid impermeable material that can be securelyjoined to the skin 328 in any manner conventionally known or by thosediscussed herein (including, but not limited to gluing, welding, heatsealing, or other means). Examples of materials useful for the tunnelvalve include polyurethane, nylon-12, and polyethylene. The tunnel valve330 can include any number of fluid transport members 332. In theillustrated variation, the valve is coupled to a conduit. However,variations include a wick type device located within the tunnel valve.

FIG. 13B shows a cross sectional view of tunnel 330 taken along line13B-13B of FIG. 13A. As shown the tunnel valve 330 forms part of thefluid transport member 332 allowing transport of fluids between theinterior/reservoir and interior of the device assembly. In certainvariations, the tunnel valve 330 can be detachable from the remainder ofthe fluid transport member 332. Upon removal, the layers of the tunnelvalve 330, as shown in FIG. 13C, close to an extent that the tunnelvalve effectively closes and prevents migration of the filler materialfrom the reservoir. In certain variations, the tunnel valve 330 fullycloses, while in other variations, the tunnel 330 can remain slightlyopen. Variations of tunnel valves include assemblies of an extruded tubeor two layers that are joined by gluing, welding, heat sealing, or othermeans at their two edges. In some variations, the tunnel valve has awall thickness between 0.001″ and 0.1″. One example of a tunnel valveincluded a thickness of 0.0015″. In additional variations, tunnel valvescan be flexible, compressible and/or deformable. In additionalvariations, layers of the tunnel valve can be reopened by the passage astructure (e.g., a conduit or other fluid transport structure).

As noted above, the tunnel valve allows for detachment of the remainderof the fluid transport member at any time, but typically once asufficient amount of fluid is delivered to the device. Removal can occurvia applying tension to a portion of the fluid transport member.Variations of the tunnel valve can employ permeable membranes, filter,or valves placed at the end of the tunnel valve to prevent dry hydrogelor other filler materials from entering the tunnel and affecting theability of the tunnel valve to seal. In some embodiments, the membraneor filter may comprise a permeable fabric such as polyester, nylon, orcellulose. In other embodiments, a valve is placed at the end of tubecomprised of a one-way duckbill or umbrella valve (available fromMiniValve of Oldenzaal, Netherlands). Alternatively, or in addition,filler material 234 can be contained in a container as discussed above,which prevents the filler material from entering the tunnel valve andswelling upon infusion of liquid, thereby clogging the valve.

Delivery System

As shown in FIG. 14, in certain variations, the device assembly can becompressed to fit within an oral dosage form 352 such as a pill,capsule, sleeve, or other form that enhances the ability of positioningthe device via ingestion or swallowing without the aid of anothermedical device. In such a case, the device 350 is contained within theoral dosage form 352 and can optionally include a tether 356. It shouldbe noted that the conduits described above can also be used as a tetheror vice versa. In any case, the tether 356 allows for controlling thedeployment location of the device 350 within the gastrointestinal tractby manipulation of the tether 356, and finally completing theadministration procedure by releasing control of the device 350, eitherby releasing the tether 356 for the patient to swallow or, moretypically, by detaching the tether from the device 350 or oral dosageform. FIG. 14 also shows a tether 356 as having two ends to allow forgreater control in positioning the device 350.

In accordance with the delivery method, a medical practitioner,typically a medically trained agent such as a physician, physician'sassistant, or nurse, administers the tethered, encapsulated payload to amammal, herein referred to as the patient. The method comprises thesimultaneous steps of directing the patient to swallow oral dosage formwhile controlling the tether. In some embodiments controlling the tethercomprises the use of a tube to transport liquid into the device, themethod also includes infusion of liquid through the tube using asyringe, pump, or other liquid delivery means. Generally, the step ofcontrolling the tether comprises, firstly, ensuring that the tether'sproximal end is retained exterior to the patient and, secondly,assisting the patient by feeding the tether into the patient's mouth andthroat at a rate compatible with the ingestion of the oral dosage form352. That is, the agent typically adjusts the feed rate of the tether sothe progress of the oral dosage form 352 down the esophagus is notimpeded by tether-induced drag while at the same time the patient doesnot feel the tether is accumulating in his or her mouth. In additionalvariations, the medical practitioner can also use the tether by securingthe section of the tether located outside of the patient's body (i.e.,to a fixture in the room or to a part of the patient).

The method further comprises an optional step of controlling thedelivery distance of the device. The delivery distance is, essentially,how far into the gastrointestinal tract the device is permitted totravel. Typical devices are designed to be deployed in the stomachalthough some devices may be designed to reach only the esophagus whilstother devices can be intended to reach the pylorus or beyond. The stepof controlling the delivery distance is best accomplished with a deviceattached to a marked tether, whereby the length of the ingested tethercorresponds to the instantaneous delivery distance, which length beingdirectly readable from a marked tether. Part of this optional step ofcontrolling the delivery distance is stopping the further ingestion ofthe tether.

In certain variations, the oral dosage form 352 dissolves upon reachingthe stomach and the fluids therein. Once free from the oral dosage form,the device 350 is free to expand into deployed state or an activeprofile. Alternatively, device 350 expands into its active profile uponinfusion of a hydrating fluid through the fluid transfer member.

Filler Material Release

One of skill in the art will note that the human GI tract is uniqueamong the abdominal viscera as it is periodically exposed to very coldand hot substances during routine alimentation. For instance, thetemperature of the stomach is known to increase to 44° C. afteringestion of a hot meal heated to 58° C. but quickly return to core bodytemperature (37-39° C.) in 20 minutes. Moreover, the temperature of thestomach can reach as high as 48° C. for between 1-2 minutes if 500milliliters of 55° C. tap water is consumed rapidly (under 2 minutes) onan empty stomach. Thus, a biocompatible material that could beeliminated by melting would ideally remain stable at core bodytemperature (37-39° C.) but melt in response to a planned interventionthat raised the temperature in the vicinity of the biocompatiblematerial to the material's melting point. In the GI tract, such amaterial would have to withstand daily fluctuations in gastrictemperature (e.g. after ingestion of a hot meal) and remain stable attemperatures between 37° C. and 44° C. but melt in response to a plannedintervention (e.g. consuming 500 milliliter of 55° C. tap water).

In some examples it was noted that one material, polycaprolactone (PCL),has been extruded into a strong monofilament (Japanese publicationJP-A05-59611 A) and has a natural melting point of 60° C., a meltingpoint that is probably not safely usable in human stomachs. However, PCLcan be modified to lower its melting point to more physiologicallyacceptable temperature. Moreover, the modified polymer can still beextruded into a strong monofilament suitable for suturing and stitchingor a film suitable for heat welding to a membrane. PCL filamentarymaterial with reduced melting temperatures (T) is available from ZeusIndustrial Products of Orangeburg, S.C., wherein 60° C.>T_(M)>45° C. byspecification.

Delivery of Thermal Exogenous Substance

In some variations the degradable material used as release material 106is allowed to degrade at its natural degradation rate in the mammaliangastric environment. In other variations, degradation is triggered oreffected by the intentional introduction of an exogenous substance 120.In additional embodiments, exogenous substance 120 is introduced orallyand at least partially in a liquid format into the stomach. In thestomach, the exogenous substance 120 mixes with the resident gastricfluid to become an immersing fluid that substantially bathes theconstruct. Alternatively, the exogenous substance 120 may be introducedinto the stomach in a solid state, as in a tablet or capsule, typicallyaccompanied by a liquid, whereby the solid is dissolved and becomes theimmersing fluid, particularly when mixed with gastric fluids. In certainembodiments extra-corporal stimulation of the exogenous substance 120may be used.

In many variations, the release material comprises modified PCLmaterial, either as a thin film for degradable patch or as a filamentarymaterial. In general, modified PCL melts at a specified meltingtemperature, T_(M) and the temperature of the stomach, T_(S), remainsbelow T_(M). The exogenous agent for PCL, therefore, comprises anelevated temperature liquid—at temperature T_(L)—which raises T_(S)above T_(M). The exogenous agent temperature T_(L) needed to raise T_(S)above T_(M) is based on the design details of entire system; that is,the means of delivery of exogenous substance 120, the design of releasematerial (that is, for example, stitches, patch or knot), and thespecified melting temperature, T_(M), of the modified PCL.

For example, an intragastric construct comprising T_(M)=48° C. modifiedPCL will degrade after the rapid ingestion of a large volume of waterwith T_(L)=55° C. Clearly, the location of the PCL release material mayaffect the rate and/or temperature at which the PCL degrades. Theextra-corporal exogenous substance 120 temperature T_(L) is higher thanthe melting temperature of the PCL to account for cooling of theformulation during transit to the stomach and due to mixing with theexistent stomach fluids and for the placement of the release material.In one example, it was found that the rapid ingestion of approximately500 milliliter of 55° C. water elevates stomach temperature T_(S) to atleast 48° C., high enough to dissolve/degrade the modified PCL and allowthe device to open and release its hydrogel contents.

In another example, an intragastric construct comprising with T_(M)=50°C. modified PCL will degrade after rapid endoscopic infusion of 500milliliter tap water with T_(L)=65° C., a temperature that is too hotfor comfortable oral ingestion but which is tolerated by the stomachwhen the liquid is delivered directly to the stomach. Alternatively, theexogenous substance 120 may be delivered directly to the stomach via anasogastric tube, again circumventing the comfort limitations of oralingestion.

In another variation, an exogenous substance can be used to raise thetemperature or otherwise change the conditions of bodily fluids toeffect release of the device. Additional variations allow for the use ofan exterior energy source to raise the temperature of the areasurrounding the device. For example, a patient can ingest a sufficientvolume of fluid, followed by the application of an external energysource (e.g., radiofrequency or ultrasound) to the exterior of thepatient's abdomen to warm the fluid within the stomach to the desiredT_(M). In another variation, the exogenous substance, e.g. elementalmagnesium, itself causes an exothermic reaction to occur in the stomach.

Yet another approach providing a exogenous substance 120 to anintragastric device comprising T_(M)=50° C. modified PCL is theingestion of 500 mL of alkaline solution (e.g. saturated sodiumbicarbonate) pre-warmed to 55° C. Said solution initiates an exothermicreaction upon neutralization with the stomach acid, warming the stomachcontents above the 50° C. PCL melting point.

Emptying and Deswelling Degradation

Certain embodiments of the present invention comprise a system for therapid degradation and volume reduction of an intragastrichydrogel-containing medical device. The system disclosed herein consistsof three paired materials: a degradable device structural element, ahydrogel and a tuned dissolution (or deswelling) solution selected todegrade the structural element and deswell the particular hydrogelaccording to their underlying chemical properties. The system isemployed in the following way: First, an intragastric device containinga hydrogel is swallowed, ingested or inserted into a patient's stomach.The hydrogel swells when exposed to fluid and takes up space within thestomach lumen. Following a sufficient residence time determined by thepatient or by an administering healthcare professional, a hydrogeldeswelling agent is ingested by or administered to the patient. Thedeswelling agent (which may be in the form of a solid, liquid, or gas)causes the device to release the enclosed hydrogel by degrading astructural element (a stitch, a line of stitches, a seam, a glue, apatch, a plug, or other known structural elements in the art). Thedeswelling agent then rapidly decreases the volume of the hydrogel tofacilitate pyloric passage and safe distal GI tract transit.

Numerous structural elements susceptible to degradation followingexposure to particular aqueous conditions are known in the art. Examplesinclude the polymer polycaprolactone which can be extruded into plaques,films, monofilaments, plugs, and other structural elements.Polycaprolactone (available from The DURECT Corporation, Birmingham,Ala.) has a melting temperature of approximately 60° C. and can bethermoformed, molded, or extruded into a number of structural elementsknown in the art. Modified PCL with melting temperatures ranging from˜40-60° C. (available from Zeus Industrial Products of Orangeburg, S.C.)can also be thermoformed, molded, or extruded into a number ofstructural elements known in the art.

Device structural elements can also be produced from materials thatselectively dissolve when exposed to elevated pH conditions, but remainsubstantially structurally intact when exposed to lower pH conditions.For example, stretch-drawn fibers can be produced from poly(methacrylicacid-co-methyl methacrylate), available as EUDRAGIT S-100, orpoly(methyl acrylate-co-methyl methacrylate-co-methacrylic acid)co-polymer, available as EUDRAGIT FS-30D, both from Evonik Industries ofDarmstadt, Germany. These polymers can be formulated with Tri EthylCitrate (TEC) and extruded into filaments which can be used to close theseams of an intragastric device. For example, a 70% EUDRAGIT S-100 and30% Tri Ethyl Citrate (available from Samrudhi Pharmachem of Mumbai,India) mix can be blended and extruded into fiber using a single screwextruder. The resulting filament can then be used to sew a seam of anintragastric device filled with hydrogel. The resulting fiber and seamremain substantially structurally stable (for example, having mechanicalproperties such as strength which do not change over time) but rapidlydegrade (for example, by dissolving) at a pH greater than about 7.

Some hydrogels may be deswelled by exposure to an aqueous solutioncomprising elevated salt concentrations. FIG. 15 illustrates thisdeswelling effect and shows the degree of swelling for severalcross-linked polyacrylic acid and cross-linked polyacrylamide hydrogelsafter exposure to solutions containing various solutes at variousconcentrations. Each subject hydrogel was loaded into a permeablepolyester mesh pouch and exposed sequentially to the listedenvironments.

Pouches were created from 9.5 cm×22.0 cm pieces of polyester mesh(available as China Silk from Ryco of Lincoln, R.I.), folded in halfalong the long edge, closed along the long edge and one short edge withfabric glue (available as Bish's Tear Mender from True Value Hardware ofCambridge, Mass.), and filled with 1.0 gram of one of the followingsuperabsorbent hydrogels: Waste Lock 770 (available from M2 PolymerTechnologies, Inc.), Waste Lock PAM (available from M2 PolymerTechnologies, Inc.), Tramfloc 1001A (available from Tramfloc of Tempe,Ariz.), Water Crystal K (available from WaterCrystals.com), Hydrosource(available from Castle International Resources of Sedona, Ariz.),poly(acrylamide-co-acrylic acid) potassium salt (available fromSigma-Aldrich), and Soil Moist (available from JRM Chemical ofCleveland, Ohio). The pouches were closed along the remaining short edgewith three square knots of a polyester sewing thread, weighed, placed ina beaker filled with 350 mL tap water, and incubated at 37 C for 1 hour.The pouch was weighed after 30 minutes and 1 hour in tap water. Thepouch was then submerged in a beaker incubated at 37 C containing 3500mL of 2% sodium chloride, blended dog food (150 grams of Adult AdvancedFitness Dry Dog Food from Hill's Science Diet blended in 50 mL simulatedgastric fluid [2 grams sodium chloride, 3.2 grams pepsin, 7 mLhydrochloric acid, brought to 1 liter with tap water], and brought to 1L with tap water), pH 3 buffer (available as Hydrion pH 3 buffer fromMicro Essential Laboratory of Brooklyn, N.Y.), and 2.5% calcium chloridefor 3.5 hours each. In between each of these incubations, the poucheswere submerged in a beaker containing 350 mL tap water incubated at 37C. The pouch was weighed after each incubation. The pouches becamelighter after each incubation in the different media but regained mostof their mass after incubation in tap water. However, in 2.5% calciumchloride, each pouch lost a significant amount of mass and could notregain this mass after incubation in tap water (data not shown).

The hydrogels shown in FIG. 15A are comprised of either cross-linkedpolyacrylic acid or cross-linked polyacrylamide, materials that arewidely used in medical device applications. As evidenced by this data,administration of a deswelling solution comprised of 2.5% CalciumChloride could rapidly decrease hydrogel volume by ten times or more.Therefore, any of the hydrogels disclosed in FIG. SGL7 paired with a2.5% Calcium Chloride deswelling solution constitute a system for ionicstrength-based construct degradation.

The hydrogels shown in FIG. 15B are comprised of either cross-linkedpolyacrylic acid or cross-linked polyacrylamide, materials that arewidely used in medical device applications. As evidenced by this data,administration of a deswelling solution comprised of 2.5 The compositionand fabrication of this hydrogel is reported in the literature(Gemeinhart, et al., 2000). As evidenced from the data, swelling extentof this hydrogel rapidly increases above pH 3. This hydrogel iscomprised of highly biocompatible materials and is therefore suitablefor ingestion by a patient as part of a space occupation device. Thehydrogel will swell in a normal gastric environment. When the device isready to be eliminated, a low pH deswelling solution could beadministered to the patient to rapidly de-swell the hydrogel.

FIG. 15C depicts the swelling performance of a chitosan/poly(vinylalcohol) superporous hydrogel in solutions at different pHs. Thecomposition and fabrication of this hydrogel is reported in theliterature (Gupta, et al., 2010). As shown in the FIG. 15C, the swellingextent of this hydrogel rapidly decreases above pH 3. This hydrogel iscomprised of highly biocompatible materials and could be swallowed by apatient as part of a space occupation device. This hydrogel is swollenwith a solution at low pH (below 3). When the device is ready to beeliminated, an elevated pH deswelling solution (pH>3) is administered tothe patient to rapidly de-swell the hydrogel.

Exemplary Embodiment 1

One embodiment of the system for rapid hydrogel construct degradationcomprises a hydrogel-containing intragastric device and deswelling agentcapable of simultaneously opening the device and deswelling thehydrogel. The construct in this exemplary embodiment is fabricated usingthe following materials: Pouches are created from 9.5 cm×22.0 cm piecesof polyester mesh (available as China Silk from Ryco of Lincoln, R.I.),folded in half along the long edge, closed along the long edge and oneshort edge with fabric glue (available as Bish's Tear Mender from TrueValue Hardware of Cambridge, Mass.), and filled with 1.0 gram of WasteLock 770 hydrogel (available from M2 Polymer Technologies, Inc.). Thepouch(es) are closed along the remaining short edge with, for example,three square knots of modified Polycaprolactone thread (available fromZeus Industrial Products of Orangeburg, S.C.) processed to melt at 47°C. The corresponding dissolution solution comprises a 2.5% CalciumChloride aqueous solution heated to 55° C. This solution degrades themodified polycaprolactone structural element (knots holding the pouchesclosed) and deswells the salt-sensitive hydrogel.

Additional Exemplary Embodiments

Additional exemplary embodiments of the system for rapid hydrogelconstruct degradation are fabricated in a similar manner to exemplaryembodiment 1. The different embodiments comprise different combinationsof “device material”, that is, the thread used to close the pouches,hydrogel material, and dissolution formulation. The table below,discloses these combinations. The following combinations are forillustrative purposes only and are not meant to be limiting unlessspecifically claimed.

Degradation Degradation Degradation Polymer Type Mode Condition TimePoly(glycolic acid) Bioabsorbable Gradual Exposure to water 2-3 monthshydrolysis or acid Poly(dioxanone) Bioabsorbable Gradual Exposure towater 6-8 months hydrolysis or acid Poly(lactic-co- BioabsorbableGradual Exposure to water 2 months glycolic acid) hydrolysis or acidPoly(vinyl alcohol) Bioabsorbable Rapid dissolution Exposure to anySeconds aqueous solution Methyacrylic acid Bioabsorbable Hydrolysis;Exposure to Days at near methyl-methacrylate on-demand alkaline pHneutral pH and co-polymers pH-dependent minutes to hours dissolution atalkaline pH Poly(caprolactone) Bioabsorbable Hydrolysis; Exposure toheat 6 months at on-demand at temperatures less temperatures thanmelting point, greater than 60° C. seconds at or above melting pointPolyester Non- None None N/A bioabsorbable Poly(propylene) Non- NoneNone N/A bioabsorbable Nylon Non- None None N/A bioabsorbable

What is claimed is:
 1. A method for temporarily occupying a gastricspace in a body of a patient, the method comprising: providing a deviceassembly having a conduit comprising a flexible end portion, where theflexible end portion extends within an enclosed reservoir of the deviceassembly; deploying the device assembly within the gastric space;delivering a filler through the conduit such that the device assemblyexpands to an active profile that occupies an increased volume withinthe gastric space; and where the device assembly further comprises asection providing a fluid path out of the reservoir, where the sectionis temporarily sealed by a release material that is located within theenclosed reservoir and remains entirely exterior to the fluid path suchthat the release material is physically separated from the gastricspace, until reduction of a structural integrity of the release materialallows opening of the section to open the fluid path.
 2. The method ofclaim 1, further comprising disengaging the conduit from the deviceassembly allowing the device assembly to self-seal.
 3. The method ofclaim 1, where the flexible end portion of the conduit is free of rigidand/or semi-rigid materials to enable swallowing of the device assemblyand the flexible end portion.
 4. The method of claim 1, where the deviceassembly further comprises a impermeable skin material, the methodfurther comprising delivering an exogenous substance to the gastricspace that causes disruption of the release material to open the sectionand allows the device assembly to reduce in size.
 5. The method of claim4, where the exogenous substance comprises a fluid having a temperaturegreater than body temperature.
 6. The method of claim 4, where theexogenous substance comprises a material that raises a temperaturewithin the gastric space.
 7. The method of claim 1, where the deviceassembly further comprises a swellable filler material within thereservoir that expands when combined with the filler, where deliveringthe filler comprises delivering the filler until the swellable fillermaterial expands the device assembly.
 8. The method of claim 7, wherethe swellable filler material comprises a hydrogel.
 9. The method ofclaim 1, where deploying the device assembly comprises deploying aplurality of device assemblies such that the plurality of deviceassemblies provide the therapeutic effect.
 10. The method of claim 1,where reduction of the structural integrity of the release material iseffected by the filler.
 11. The method of claim 1, where the releasematerial is mechanically coupled to a portion of the section forming thefluid path.